ASCO 2025 | Guidance on the optimal use of novel agents for lower-risk and intermediate-risk MDS

What I would like to tell you today is what I did during ASCO. The American Society of Clinical Oncology this year just gave more space to myelodysplastic syndrome. There was a specific educational session that created a lot of interest and there was a good audience. The subject of this educational session was how to classify and how to stratify prognostically myelodysplastic syndromes, how to use IPSS-M and IPSS-R as tools to choose the best therapy, how they impact on the choice of therapy. And my specific subject, I was chairing the entire educational session, but my specific subject was to make some order, let’s say, on the novel approvals of agents for low-risk and intermediate-risk MDS. In fact, now we have several agents, luspatacept since 2020, but more recently, 2023, for first-line patients who received only transfusions and were never treated with erythropoietin or erythropoietic stimulating agents. And then also the approval of imetelstat again for transfusion-dependent anemic transfusion-dependent lower-risk MDS patients and therefore there is the need to explain how to schedule this treatment, how long and with which dosage and for which patients. So we have new tools, we have to understand how to optimize their use. So in this sense, I discussed how to use luspatacept in transfusion-dependent patients, not only ring sideroblast or SF3B1-positive ones, but all the low-risk MDS patients. Because what has been shown is that the duration of transfusion independence induced by luspatacept is significantly longer than that induced by erythropoietic stimulating agents and it’s also correlating with a prolongation of survival. So this is quite important and it is also very important to keep in mind that either if we start with one milligram per kilogram every three weeks we have to increase and escalate the dose to 1.75 in case the patients do not respond immediately with transfusion independence. And then what was very interesting was also to discuss the choice of imetelstat in patients transfusion-dependent with low-risk MDS. This agent is particularly active in inducing transfusion independence in patients who have a very high transfusion burden. It has been shown that with respect to placebo, imetelstat can induce 40% of transfusion independence. And overall, 18% of treated patients have a longer transfusion independence longer than one year. So it is a very important result. And what is very important is that we never had such an agent active in high transfusion burden patients. And on top of that, imetelstat has disease-modifying activity, decreasing the variant allele frequency of the somatic mutation present in this kind of patients. Moreover, imetelstat seems to be active also as third-line therapy, not only after ESAs, as in the Phase III study, but also for patients who received lenalidomide or luspatacept even. So it is a further choice for us for patients who lose response to previous treatment.

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